Fine-tuning BACH2 dosage balances stemness and effector function to enhance antitumor T cell therapy
University of Cambridge · Cambridge School · +8 more institutions
Abstract
Adoptive T cell therapies are limited by poor persistence of transferred cells. Attempts to enhance persistence have focused on genetic induction of constitutively hyperactivated but potentially oncogenic T cell states. Physiological T cell responses are maintained by quiescent stem-like/memory cells dependent upon the transcription factor BACH2. Here we show that quantitative control of BACH2 dosage regulates differentiation along the continuum of stem and effector CD8⁺ T cell states, enabling engineering of synthetic states with persistent antitumor activity. While conventional high-level overexpression of BACH2 enforces quiescence and hinders tumor control, low-dose BACH2 expression promotes persistence…
Citation impact
- FWCI
- 97.03
- Percentile
- 100%
- References
- 62
Authors
25Topics & keywords
- Effector
- Transcription factor
- T cell
- Cell
- Cell therapy
- Function (biology)
- Stem cell
- Cellular differentiation
Funding
- CRCancer Research UK
- ECEuropean CommissionAward: EP/X024709/1
- ACAustralian Cancer Research Foundation
- FAFondation ARC pour la Recherche sur le Cancer
- PMPeter MacCallum Cancer Centre
- MRMedical Research CouncilAwards: MR/W018454/1, MR/Y013301/1
- BABiotechnology and Biological Sciences Research CouncilAwards: BB/Z516132/1, BB/X006344/1